T1D, T2D, and MODY

Supplementary materials

Supplementary Table 1. The most significant obesity genes that are common between the different types of diabetes; T1D, T2D, and MODY.

Genes Genes Genes Genes VDR BDNF PPARGC1A SERPINC1 ACE IFNG SERPINE1 APOA1 HMGCR ABCA1 CYP19A1 CCK MMP2 RETN VCAM1 ADRB2 EDN1 IL4 TP53 GAPDH ABCB7 BCHE TNF APC GSR BCL2 INSR TLR2 FASLG TNFRSF11B IFNA1 VEGFA GGT1 CD36 HNF1B CDKN2A CYBA FGF2 GNRH1 TGFB1 IGF1 CLU HLA-DRB1 KCNJ11 CCL11 PCK2 IL1A TFRC PTEN HK2 LDLR ABCC8 HMOX1 G6PD LPL GAST HNF1A TF CAT TSHR NOS2 GCK MPO JUN INS IGF1R TCF7L2 HCRT FLT1 IRS1 LIPC SERPINF2 SLC6A4 GHRL SELP TIMP1 SOD2 ICAM1 GCG CSF2 BGLAP RECK F5 GHRH MMP3 RPS27A IL8 MMP9 PPARA TNFRSF1B HLA-A CD14 NGF APOB SLC2A2 ADIPOQ GATA3 CS AKT1 IL2RA LTF PIK3R1 PAX4 IL5 GRP TTR AGT NR1H2 LEP CGA TNFRSF1A PTPRN2 PPARG STAT3 OXT HNF4A SPP1 CYP1A2 CRP F2 TG HIF1A PTGS2 CYP2C19 CALCA AHSG NOS1 SERPINA1 B2M CRH NOS3 LRP5 IL10 MAPT OLR1 PRL GLP1R GH1 IGF2 CASR ITGB3 IAPP CNR1 CYP2C9 MTHFR DKK1 IL1B ISL1 NFE2L2 REN PAX6 NR3C1 VWF TNFSF11 HP NPY GHR OPRM1 IL18 DPP4 CYP17A1 GAD2 NPPB TLR4 IGFBP2 APOC3 LEPR AR SOD1 BMP6 GAD1 IFNA2 NPPA PCSK9 CD79A ESR1 EPO FOXM1 SST ACHE PIK3CA PRF1 CP APOE BMP4 KLK3 IL2 NEUROD1 IL1R1 FAS SPARC CCL2 C3 AGTR1 HGF PDX1 IGFBP3 IL6 PON1 ALB APP NEUROG3 PTGS1 CPT2 FOXA2 LCAT COMT IGFBP1 APOA4 UCP2 HSPD1 POMC PROC

Supplementary Table 2. Involved GO terms from ClueGo enrichment analysis for cluster 1 genes.

Group p-Value Corrected with % Associated Nr. GO ID GO Term Associated Genes Found Bonferroni step Genes Genes down [AGT, AGTR1, APLN, APLNR, APP, BDKRB2, C3, CCK, CCKAR, Peptide ligand-binding CCL5, CCR2, CCR5, CX3CR1, CXCL5, CXCL8, CXCR4, EDN1, R-HSA:375276 7.15293E-47 18.42 35.00 receptors EDNRA, F2, GAL, GHSR, GRP, HCRT, KNG1, MLN, NPY, NTS, OPRM1, OXT, POMC, PPY, PYY, SST, TAC1, TRH] [ADORA1, ADRA2A, ADRA2B, AGT, AGTR1, APLN, APLNR, APP, BDKRB2, C3, CCK, CCKAR, CCL5, CCR2, CCR5, CNR1, Class A/1 (Rhodopsin- CNR2, CX3CR1, CXCL5, CXCL8, CXCR4, DRD2, DRD4, EDN1, R-HSA:373076 7.15293E-47 14.81 48.00 like receptors) EDNRA, F2, GAL, GHSR, GNRH1, GPR39, GRP, HCRT, HTR1A, HTR2A, KNG1, MLN, MTNR1A, MTNR1B, NPY, NTS, OPRM1, OXT, POMC, PPY, PYY, SST, TAC1, TRH] [ADORA1, ADRA2A, ADRA2B, AGT, AGTR1, APLN, APLNR, BDKRB2, C3, CCK, CCKAR, CNR1, CNR2, DRD2, DRD4, EDN1, Neuroactive ligand- KEGG:04080 7.15293E-47 12.13 41.00 EDNRA, F2, GAL, GCG, GCGR, GHSR, GNRH1, GRP, HCRT, receptor interaction HTR1A, HTR2A, KNG1, MLN, MTNR1A, MTNR1B, NPY, NTS, OPRM1, OXT, POMC, PPY, PYY, SST, TAC1, TRH] [ADORA1, ADRA2A, ADRA2B, AGT, AGTR1, APLN, APLNR, APP, BDKRB2, C3, CASR, CCK, CCKAR, CCL5, CCR2, CCR5, CNR1, CNR2, CX3CR1, CXCL5, CXCL8, CXCR4, DRD2, DRD4, R-HSA:500792 GPCR ligand binding 7.15293E-47 11.16 51.00 EDN1, EDNRA, F2, GAL, GCG, GCGR, GHSR, GNRH1, GPR39, GRP, HCRT, HTR1A, HTR2A, KNG1, MLN, MTNR1A, MTNR1B, NPY, NTS, OPRM1, OXT, POMC, PPY, PYY, SST, TAC1, TRH] [ADORA1, ADRA2A, ADRA2B, AGT, APLN, APLNR, APOA1, APOA2, APOB, APOE, APP, BDKRB2, C3, CASR, CCL5, CCR2, G alpha (i) signalling R-HSA:418594 7.15293E-47 9.09 37.00 CCR5, CNR1, CNR2, CX3CR1, CXCL5, CXCL8, CXCR4, DRD2, events DRD4, GAL, GNAI1, HTR1A, KNG1, MTNR1A, MTNR1B, NPY, OPRM1, POMC, PPY, PYY, SST] [AHSG, ALB, APOA1, APOA2, APOA5, APOB, APOE, APP, Post-translational protein BMP4, C3, CP, CSF1, CST3, F5, FGA, FGF23, IGFBP1, IGFBP3, R-HSA:8957275 7.24486E-42 28.70 31.00 phosphorylation IGFBP5, IGFBP7, IL6, KNG1, PCSK9, PNPLA2, PROC, SERPINA1, SERPINC1, SPP1, TF, TIMP1, TNC] Regulation of Insulin-like [AHSG, ALB, APOA1, APOA2, APOA5, APOB, APOE, APP, R-HSA:381426 Growth Factor (IGF) 7.24486E-42 25.60 32.00 BMP4, C3, CP, CSF1, CST3, F2, F5, FGA, FGF23, IGFBP1, IGFBP3, transport and uptake by Insulin-like Growth IGFBP5, IGFBP7, IL6, KNG1, PCSK9, PNPLA2, PROC, SERPINA1, Factor Binding Proteins SERPINC1, SPP1, TF, TIMP1, TNC] (IGFBPs) [AGT, AGTR1, APP, BDKRB2, CASR, CCK, CCKAR, EDN1, G alpha (q) signalling EDNRA, F2, GAST, GCG, GCGR, GHSR, GNRH1, GPR39, GRP, R-HSA:416476 6.88134E-26 12.44 27.00 events HCRT, HTR2A, KNG1, MLN, NTS, OXT, PIK3CA, PIK3R1, TAC1, TRH] Adrenaline signalling R-HSA:392023 through Alpha-2 6.72026E-10 66.67 2.00 [ADRA2A, ADRA2B] adrenergic receptor R-HSA:390651 Dopamine receptors 6.72026E-10 40.00 2.00 [DRD2, DRD4] Common Pathway of R-HSA:140875 6.72026E-10 22.73 5.00 [F2, F5, FGA, PROC, SERPINC1] Fibrin Clot Formation R-HSA:390696 Adrenoceptors 6.72026E-10 22.22 2.00 [ADRA2A, ADRA2B] R-HSA:390666 Serotonin receptors 6.72026E-10 16.67 2.00 [HTR1A, HTR2A] Amine ligand-binding R-HSA:375280 6.72026E-10 14.29 6.00 [ADRA2A, ADRA2B, DRD2, DRD4, HTR1A, HTR2A] receptors Platelet Aggregation (Plug R-HSA:76009 6.72026E-10 10.26 4.00 [ADRA2A, ADRA2B, F2, FGA] Formation) Common Pathway of R-HSA:140875 1.1004E-08 22.73 5.00 [F2, F5, FGA, PROC, SERPINC1] Fibrin Clot Formation Transport of gamma- carboxylated protein R-HSA:159763 precursors from the 1.1004E-08 22.22 2.00 [F2, PROC] endoplasmic reticulum to the Golgi apparatus Gamma-carboxylation of R-HSA:159740 1.1004E-08 20.00 2.00 [F2, PROC] protein precursors Removal of aminoterminal R-HSA:159782 1.1004E-08 20.00 2.00 [F2, PROC] propeptides from gamma- carboxylated proteins Intrinsic Pathway of R-HSA:140837 1.1004E-08 18.18 4.00 [F2, KNG1, PROC, SERPINC1] Fibrin Clot Formation Gamma-carboxylation, transport, and amino- R-HSA:159854 1.1004E-08 18.18 2.00 [F2, PROC] terminal cleavage of proteins Formation of Fibrin Clot R-HSA:140877 1.1004E-08 15.38 6.00 [F2, F5, FGA, KNG1, PROC, SERPINC1] (Clotting Cascade) Complement and KEGG:04610 1.1004E-08 11.39 9.00 [BDKRB2, C3, F2, F5, FGA, KNG1, PROC, SERPINA1, SERPINC1] coagulation cascades Platelet Aggregation (Plug R-HSA:76009 1.1004E-08 10.26 4.00 [ADRA2A, ADRA2B, F2, FGA] Formation) Binding and entry of HIV R-HSA:173107 2.31219E-08 20.00 2.00 [CCR5, CXCR4] virion R-HSA:6783783 Interleukin-10 signaling 2.31219E-08 14.89 7.00 [CCL5, CCR2, CCR5, CSF1, CXCL8, IL6, TIMP1] Chemokine receptors R-HSA:380108 2.31219E-08 14.58 7.00 [CCL5, CCR2, CCR5, CX3CR1, CXCL5, CXCL8, CXCR4] bind chemokines Early Phase of HIV Life R-HSA:162594 2.31219E-08 10.00 2.00 [CCR5, CXCR4] Cycle Chagas disease (American KEGG:05142 3.50978E-07 8.74 9.00 [BDKRB2, C3, CCL5, CXCL8, GNAI1, IL6, KNG1, PIK3CA, PIK3R1] trypanosomiasis) KEGG:04614 Renin-angiotensin system 0.000272724 8.70 2.00 [AGT, AGTR1] KEGG:04924 Renin secretion 0.000272724 8.70 6.00 [ADORA1, AGT, AGTR1, EDN1, EDNRA, GNAI1] R-HSA:8963901 Chylomicron remodeling 0.000437865 55.56 5.00 [APOA1, APOA2, APOA5, APOB, APOE] R-HSA:8963888 Chylomicron assembly 0.000437865 44.44 4.00 [APOA1, APOA2, APOB, APOE] R-HSA:8964026 Chylomicron clearance 0.000437865 40.00 2.00 [APOB, APOE] Scavenging by Class B R-HSA:3000471 0.000437865 33.33 2.00 [APOA1, APOB] Receptors R-HSA:8964058 HDL remodeling 0.000437865 30.00 3.00 [ALB, APOA1, APOE] Plasma lipoprotein R-HSA:8963898 0.000437865 22.22 4.00 [APOA1, APOA2, APOB, APOE] assembly Plasma lipoprotein R-HSA:8963899 0.000437865 20.00 6.00 [ALB, APOA1, APOA2, APOA5, APOB, APOE] remodeling Scavenging by Class A R-HSA:3000480 0.000437865 15.79 3.00 [APOA1, APOB, APOE] Receptors Scavenging of heme from R-HSA:2168880 0.000437865 15.38 2.00 [ALB, APOA1] plasma Plasma lipoprotein R-HSA:8964043 0.000437865 12.12 4.00 [APOA1, APOB, APOE, PCSK9] clearance Regulation of TLR by R-HSA:5686938 0.000437865 10.53 2.00 [APOB, FGA] endogenous ligand R-HSA:8964038 LDL clearance 0.000437865 10.53 2.00 [APOB, PCSK9] Plasma lipoprotein R-HSA:174824 assembly, remodeling, and 0.000437865 10.14 7.00 [ALB, APOA1, APOA2, APOA5, APOB, APOE, PCSK9] clearance KEGG:04979 Cholesterol metabolism 0.000437865 10.00 5.00 [APOA1, APOA2, APOB, APOE, PCSK9] Binding and Uptake of R-HSA:2173782 Ligands by Scavenger 0.000437865 9.52 4.00 [ALB, APOA1, APOB, APOE] Receptors Retinoid metabolism and R-HSA:975634 0.000437865 9.30 4.00 [APOA1, APOA2, APOB, APOE] transport Metabolism of fat-soluble R-HSA:6806667 0.000437865 8.51 4.00 [APOA1, APOA2, APOB, APOE] vitamins Vitamin digestion and KEGG:04977 0.000437865 8.33 2.00 [APOA1, APOB] absorption MET activates R-HSA:8851907 0.004786962 33.33 2.00 [PIK3CA, PIK3R1] PI3K/AKT signaling Activated NTRK3 signals R-HSA:9603381 0.004786962 33.33 2.00 [PIK3CA, PIK3R1] through PI3K Activated NTRK2 signals R-HSA:9028335 0.004786962 28.57 2.00 [PIK3CA, PIK3R1] through PI3K R-HSA:198203 PI3K/AKT activation 0.004786962 22.22 2.00 [PIK3CA, PIK3R1] PI3K events in ERBB4 R-HSA:1250342 0.004786962 20.00 2.00 [PIK3CA, PIK3R1] signaling Signaling by FGFR3 R-HSA:8853334 0.004786962 20.00 2.00 [PIK3CA, PIK3R1] fusions in cancer Signaling by FGFR4 in R-HSA:5655291 0.004786962 18.18 2.00 [PIK3CA, PIK3R1] disease R-HSA:5654710 PI-3K cascade:FGFR3 0.004786962 16.67 3.00 [FGF23, PIK3CA, PIK3R1] Erythropoietin activates R-HSA:9027276 Phosphoinositide-3- 0.004786962 16.67 2.00 [PIK3CA, PIK3R1] kinase (PI3K) R-HSA:5654720 PI-3K cascade:FGFR4 0.004786962 15.00 3.00 [FGF23, PIK3CA, PIK3R1] R-HSA:5654689 PI-3K cascade:FGFR1 0.004786962 14.29 3.00 [FGF23, PIK3CA, PIK3R1] Signaling by FGFR3 in R-HSA:5655332 0.004786962 13.64 3.00 [FGF23, PIK3CA, PIK3R1] disease Signaling by FGFR3 point R-HSA:8853338 0.004786962 13.64 3.00 [FGF23, PIK3CA, PIK3R1] mutants in cancer Constitutive Signaling by R-HSA:5637810 0.004786962 13.33 2.00 [PIK3CA, PIK3R1] EGFRvIII Signaling by EGFRvIII in R-HSA:5637812 0.004786962 13.33 2.00 [PIK3CA, PIK3R1] Cancer R-HSA:5654695 PI-3K cascade:FGFR2 0.004786962 13.04 3.00 [FGF23, PIK3CA, PIK3R1] PI3K events in ERBB2 R-HSA:1963642 0.004786962 12.50 2.00 [PIK3CA, PIK3R1] signaling Role of R-HSA:2730905 LAT2/NTAL/LAB on 0.004786962 12.50 2.00 [PIK3CA, PIK3R1] calcium mobilization Downstream signaling of R-HSA:5654708 0.004786962 12.00 3.00 [FGF23, PIK3CA, PIK3R1] activated FGFR3 R-HSA:180292 GAB1 signalosome 0.004786962 11.76 2.00 [PIK3CA, PIK3R1] Signaling by NTRK3 R-HSA:9034015 0.004786962 11.76 2.00 [PIK3CA, PIK3R1] (TRKC) Signaling by cytosolic R-HSA:1839117 0.004786962 11.11 2.00 [PIK3CA, PIK3R1] FGFR1 fusion mutants R-HSA:210993 Tie2 Signaling 0.004786962 11.11 2.00 [PIK3CA, PIK3R1] Downstream signaling of R-HSA:5654716 0.004786962 11.11 3.00 [FGF23, PIK3CA, PIK3R1] activated FGFR4 Regulation of lipolysis in KEGG:04923 0.004786962 10.91 6.00 [ADORA1, GNAI1, NPY, PIK3CA, PIK3R1, PNPLA2] adipocytes Constitutive Signaling by R-HSA:1236382 Ligand-Responsive 0.004786962 10.53 2.00 [PIK3CA, PIK3R1] EGFR Cancer Variants Signaling by Ligand- R-HSA:5637815 Responsive EGFR 0.004786962 10.53 2.00 [PIK3CA, PIK3R1] Variants in Cancer Downstream signaling of R-HSA:5654696 0.004786962 10.00 3.00 [FGF23, PIK3CA, PIK3R1] activated FGFR2 FGFR1 mutant receptor R-HSA:1839124 0.004786962 9.68 3.00 [FGF23, PIK3CA, PIK3R1] activation Downstream signaling of R-HSA:5654687 0.004786962 9.68 3.00 [FGF23, PIK3CA, PIK3R1] activated FGFR1 CD28 dependent R-HSA:389357 0.004786962 9.09 2.00 [PIK3CA, PIK3R1] PI3K/Akt signaling Regulation of signaling by R-HSA:912631 0.004786962 9.09 2.00 [PIK3CA, PIK3R1] CBL Nephrin family R-HSA:373753 0.004786962 8.70 2.00 [PIK3CA, PIK3R1] interactions Signaling by EGFR in R-HSA:1643713 0.004786962 8.00 2.00 [PIK3CA, PIK3R1] Cancer Role of phospholipids in R-HSA:2029485 0.004786962 8.00 2.00 [PIK3CA, PIK3R1] phagocytosis Signaling by NTRK2 R-HSA:9006115 0.004786962 8.00 2.00 [PIK3CA, PIK3R1] (TRKB) Signaling by R-HSA:9006335 0.004786962 8.00 2.00 [PIK3CA, PIK3R1] Erythropoietin FOXO-mediated transcription of oxidative R-HSA:9615017 0.005339022 10.34 3.00 [IGFBP1, NPY, POMC] stress, metabolic and neuronal genes R-HSA:202040 G-protein activation 0.005773145 10.71 3.00 [GNAI1, OPRM1, POMC] KEGG:05143 African trypanosomiasis 0.006542366 8.11 3.00 [APOA1, IL6, KNG1] R-HSA:380994 ATF4 activates genes 0.013149546 8.00 2.00 [CXCL8, IGFBP1] Synthesis, secretion, and R-HSA:381771 inactivation of Glucagon- 0.022380594 10.00 2.00 [GCG, GRP] like Peptide-1 (GLP-1) Incretin synthesis, R-HSA:400508 0.022380594 8.70 2.00 [GCG, GRP] secretion, and inactivation

Supplementary Table 3. Involved GO terms from ClueGo enrichment analysis for cluster 2 genes.

Term p-Value % GO ID GO Term Corrected with Associated Nr. Genes Associated Genes Found Bonferroni step down Genes [A2M, CLU, F13A1, FGB, HGF, IGF1, IGF2, PROS1, R-HSA:114608 Platelet degranulation 3.48546E-20 11.63 15.00 SERPINE1, SERPINF2, SPARC, TGFB1, THBS1, VEGFA, VWF] [A2M, CLU, F13A1, FGB, HGF, IGF1, IGF2, PROS1, Response to elevated platelet R-HSA:76005 5.87143E-20 11.19 15.00 SERPINE1, SERPINF2, SPARC, TGFB1, THBS1, cytosolic Ca2+ VEGFA, VWF] Class B/2 (Secretin family [ADM, CALCA, CRH, GHRH, GIP, GLP1R, GNAS, R-HSA:373080 9.2479E-13 10.53 10.00 receptors) IAPP, PTH, RAMP1] Complement and coagulation [A2M, CLU, F13A1, FGB, PROS1, SERPINE1, KEGG:04610 4.78905E-10 10.13 8.00 cascades SERPINF2, VWF] KEGG:04923 Regulation of lipolysis in adipocytes 9.30048E-08 10.91 6.00 [ADRB1, ADRB2, ADRB3, CGA, GNAS, TSHR] R-HSA:419812 Calcitonin-like ligand receptors 1.06302E-07 40.00 4.00 [ADM, CALCA, IAPP, RAMP1] Formation of Fibrin Clot (Clotting R-HSA:140877 6.20737E-07 12.82 5.00 [A2M, F13A1, FGB, PROS1, VWF] Cascade) R-HSA:390696 Adrenoceptors 1.26179E-05 33.33 3.00 [ADRB1, ADRB2, ADRB3] R-HSA:420092 Glucagon-type ligand receptors 1.31787E-05 12.12 4.00 [GHRH, GIP, GLP1R, GNAS] Common Pathway of Fibrin Clot R-HSA:140875 0.000161063 13.64 3.00 [F13A1, FGB, PROS1] Formation TFAP2 (AP-2) family regulates R-HSA:8866910 transcription of growth factors and 0.00082292 13.33 2.00 [CGA, VEGFA] their receptors GRB2:SOS provides linkage to R-HSA:354194 0.00082292 13.33 2.00 [FGB, VWF] MAPK signaling for Integrins p130Cas linkage to MAPK R-HSA:372708 0.00082292 13.33 2.00 [FGB, VWF] signaling for integrins SHC-related events triggered by R-HSA:2428933 0.001140851 22.22 2.00 [IGF1, IGF2] IGF1R R-HSA:75205 Dissolution of Fibrin Clot 0.001227039 15.38 2.00 [SERPINE1, SERPINF2] R-HSA:375281 Hormone ligand-binding receptors 0.001560206 16.67 2.00 [CGA, TSHR]

Supplementary Table 4. Involved GO terms from ClueGo enrichment analysis for cluster 3 genes.

Term p-Value Corrected with % Associated Nr. GO ID GO Term Associated Genes Found Bonferroni step Genes Genes down R-HSA:74749 Signal attenuation 1.00541E-07 40.00 4.00 [INS, INSR, IRS1, SHC1] R-HSA:74749 Signal attenuation 1.00541E-07 40.00 4.00 [INS, INSR, IRS1, SHC1] KEGG:04910 Insulin signaling pathway 2.53779E-07 5.11 7.00 [INPPL1, INS, INSR, IRS1, PRKCZ, PTPN1, SHC1] Cargo recognition for clathrin-mediated R-HSA:8856825 1.85804E-06 5.66 6.00 [IGF2R, LDLR, RPS27A, SH3GL2, TFRC, WNT5A] endocytosis R-HSA:74713 IRS activation 2.49046E-06 60.00 3.00 [INS, INSR, IRS1] R-HSA:432722 Golgi Associated Vesicle Biogenesis 2.59797E-06 8.93 5.00 [FTH1, IGF2R, PIK3C2A, SH3GL2, TFRC] R-HSA:199992 trans-Golgi Network Vesicle Budding 9.03152E-06 6.94 5.00 [FTH1, IGF2R, PIK3C2A, SH3GL2, TFRC] R-HSA:421837 Clathrin derived vesicle budding 9.03152E-06 6.94 5.00 [FTH1, IGF2R, PIK3C2A, SH3GL2, TFRC] KEGG:04930 Type II diabetes mellitus 6.23421E-05 8.70 4.00 [INS, INSR, IRS1, PRKCZ] Interleukin-3, Interleukin-5 and GM-CSF R-HSA:512988 7.17434E-05 8.33 4.00 [IL5, INPPL1, RPS27A, SHC1] signaling KEGG:04913 Ovarian steroidogenesis 7.54143E-05 8.16 4.00 [IGF1R, INS, INSR, LDLR] R-HSA:74751 Insulin receptor signalling cascade 0.00010795 7.41 4.00 [INS, INSR, IRS1, SHC1] R-HSA:74751 Insulin receptor signalling cascade 0.00010795 7.41 4.00 [INS, INSR, IRS1, SHC1] KEGG:04213 Longevity regulating pathway 0.000181635 6.45 4.00 [IGF1R, INS, INSR, IRS1] R-HSA:6807004 Negative regulation of MET activity 0.00024795 14.29 3.00 [PTPN1, RPS27A, SH3GL2] R-HSA:74752 Signaling by Insulin receptor 0.000420816 5.13 4.00 [INS, INSR, IRS1, SHC1] R-HSA:74752 Signaling by Insulin receptor 0.000420816 5.13 4.00 [INS, INSR, IRS1, SHC1] R-HSA:6806834 Signaling by MET 0.000424953 5.06 4.00 [PTPN1, RPS27A, SH3GL2, SHC1] R-HSA:912526 Interleukin receptor SHC signaling 0.000478543 11.11 3.00 [IL5, INPPL1, SHC1] R-HSA:1592389 Activation of Matrix Metalloproteinases 0.000847019 9.09 3.00 [MMP8, MMP9, TIMP2] Aldosterone-regulated sodium KEGG:04960 0.001145307 8.11 3.00 [INS, INSR, IRS1] reabsorption R-HSA:451927 Interleukin-2 family signaling 0.001841966 6.82 3.00 [IL5, INPPL1, SHC1] R-HSA:177929 Signaling by EGFR 0.002418122 6.12 3.00 [RPS27A, SH3GL2, SHC1] R-HSA:2428933 SHC-related events triggered by IGF1R 0.002535729 22.22 2.00 [IGF1R, SHC1] R-HSA:2428933 SHC-related events triggered by IGF1R 0.002535729 22.22 2.00 [IGF1R, SHC1] KEGG:04923 Regulation of lipolysis in adipocytes 0.002696766 5.45 3.00 [INS, INSR, IRS1] Signaling by Type 1 Insulin-like Growth R-HSA:2404192 0.002723271 5.56 3.00 [IGF1R, IRS1, SHC1] Factor 1 Receptor (IGF1R) Signaling by Type 1 Insulin-like Growth R-HSA:2404192 0.002723271 5.56 3.00 [IGF1R, IRS1, SHC1] Factor 1 Receptor (IGF1R) R-HSA:2428924 IGF1R signaling cascade 0.002736368 5.66 3.00 [IGF1R, IRS1, SHC1] R-HSA:2428924 IGF1R signaling cascade 0.002736368 5.66 3.00 [IGF1R, IRS1, SHC1] R-HSA:1236977 Endosomal/Vacuolar pathway 0.002790979 18.18 2.00 [B2M, CTSS] KEGG:04216 Ferroptosis 0.002937287 5.00 2.00 [FTH1, TFRC] R-HSA:5654741 Signaling by FGFR3 0.002937287 5.00 2.00 [RPS27A, SHC1] R-HSA:917937 Iron uptake and transport 0.002948518 5.17 3.00 [FTH1, RPS27A, TFRC] R-HSA:182971 EGFR downregulation 0.005312053 6.45 2.00 [RPS27A, SH3GL2] TGF-beta receptor signaling in EMT R-HSA:2173791 0.005586252 12.50 2.00 [PRKCZ, RPS27A] (epithelial to mesenchymal transition) InlB-mediated entry of Listeria R-HSA:8875360 0.005586252 12.50 2.00 [RPS27A, SH3GL2] monocytogenes into host cell R-HSA:76009 Platelet Aggregation (Plug Formation) 0.005587752 5.13 2.00 [PTPN1, SHC1] R-HSA:9034015 Signaling by NTRK3 (TRKC) 0.005796306 11.76 2.00 [IRS1, SHC1] R-HSA:9034015 Signaling by NTRK3 (TRKC) 0.005796306 11.76 2.00 [IRS1, SHC1] Constitutive Signaling by Ligand- R-HSA:1236382 0.006609053 10.53 2.00 [RPS27A, SHC1] Responsive EGFR Cancer Variants Signaling by Ligand-Responsive EGFR R-HSA:5637815 0.006609053 10.53 2.00 [RPS27A, SHC1] Variants in Cancer R-HSA:2424491 DAP12 signaling 0.006633994 6.67 2.00 [B2M, SHC1] R-HSA:354192 Integrin alphaIIb beta3 signaling 0.006716084 7.41 2.00 [PTPN1, SHC1] R-HSA:9006921 Integrin signaling 0.006716084 7.41 2.00 [PTPN1, SHC1] R-HSA:77387 Insulin receptor recycling 0.007471563 7.69 2.00 [INS, INSR] Listeria monocytogenes entry into host R-HSA:8876384 0.008005403 9.09 2.00 [RPS27A, SH3GL2] cells R-HSA:1643713 Signaling by EGFR in Cancer 0.008056271 8.00 2.00 [RPS27A, SHC1] R-HSA:982772 Growth hormone receptor signaling 0.008481092 8.33 2.00 [IRS1, PTPN1]